The increasingly frequent outbreaks of pathogenic viruses have underlined the urgent need to improve our arsenal of antivirals that can be deployed for future pandemics. Innate immunity is a powerful first line of defense against pathogens, and compounds that boost the innate response have high potential to act as broad-spectrum antivirals. Here, we harnessed localization-dependent protein-complementation assays (called Alpha Centauri) to measure the nuclear translocation of interferon regulatory factors (IRFs), thus providing a readout of innate immune activation following viral infection that is applicable to high-throughput screening of immunomodulatory molecules. As proof of concept, we screened a library of kinase inhibitors on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identified Gilteritinib as a powerful enhancer of innate responses to viral infection. This immunostimulatory activity of Gilteritinib was found to be dependent on the AXL-IRF7 axis and results in a broad and potent antiviral activity against unrelated RNA viruses.

越来越频繁的致病病毒爆发突显出迫切需要改进我们的抗病毒药物库，以应对未来的大流行病。先天免疫是抵御​​病原体的强大第一道防线，增强先天反应的化合物具有作为广谱抗病毒药物的巨大潜力。在这里，我们利用定位依赖性蛋白质互补测定（称为半人马座阿尔法）来测量干扰素调节因子 (IRF) 的核转位，从而提供病毒感染后先天免疫激活的读数，适用于免疫调节的高通量筛选分子。作为概念证明，我们筛选了一个针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染的激酶抑制剂库，并确定 Gilteritinib 是对病毒感染的先天反应的强大增强剂。Gilteritinib 的这种免疫刺激活性被发现依赖于 AXL-IRF7 轴，并导致针对无关 RNA 病毒的广泛而有效的抗病毒活性。